delta 4, 5-unsaturated androstene compound and process of making same



Patented May 23, 1939 UNITED STATES PATENT OFFICE A -UNSATURATED ANDROSTENE COM- POUND AND PROCESS OF MAKING SAME No Drawing. Application September 8, 1936, Se-

rial No. 99,860. In Switzerland November 4,

6 Claims.

This invention is based on the observation that the double carbon bond of A '-dehydroandrosterone can be shifted to the A -position by combining the compound with hydrogen halide and then eliminating the hydrogen halide,

Instead of dehydroandrosterone, compounds derived therefrom, for instance androstenecliol- (3,17) or l7-methyl-androstene-diol-(3,17) as well as esters or ethers of these cyclic alcohols, can be similarly isomerized.

The elimination of hydrogen halide must be conducted under mild conditions in order to avoid a reversion of the double bond. The alkali metal salts of organic acids, for instance an alkali metal acetate, are particularly suitable for this purpose.

The new compounds find application in therapeutics.

' The following examples illustrate the invention:

Example 1 2 grams of A -trans-dehydroandrosterone are dissolved in 500 cc. of absolute ether and the solution is mixed with 500 cc. of a solution of hydrogen chloride in absolute alcohol saturated at C. The mixture is allowed to stand for about 2 days at room temperature, or while cooling, and finally cautiously evaporated ina vacuum. The transdehydroandrosterone hydrochloride separates in the form of colorless crystals of melting point 156.5 to 157 C. It is freely soluble in petroleum ether, chloroform and benzene but sparingly soluble in alcohol.

2 grams of this hydrochloride are dissolved in 500 cc, of absolute alcohol and, after addition of 4 grams of freshly fused potassium acetate, the whole is heated on the water-bath for 6 hours. Potassium chloride separates. After addition of water the product of the reaction is extracted by means of ether. The ethereal solution is washed with water, then dried over sodium sulfate and evaporated in a vacuum. The residue is purified by recrystallization from hexane. The A -transdehydroandrosterone forms colorless needles of melting point 129 to 130 C.

Instead of the hydrochloride the hydrobromide or hydroiodide of dehydroandrosterone may be used for the isomerization.

Example 2 5 grams of A -androstene-al'l-diol are treated ethers, such as for example the methyl or ethyl 1 ethers.

What I claim is: 1. The M -unsaturated 3-hydroxy androstenecompounds.

2. Th A -trans-dehydroandrosterone of the formula H Ho melting at 129 to 130 C.

3. The A -androstene-3,17-diol of the formula CH3- CH:

lL0H

melting at 158 C.

4. A process for the manufacture of A -androstene compounds, consisting in combining A androstene compounds with hydrogen halide and then eliminating the hydrogen halide under mild conditions with alkali metal salts of organic acids.

5. A process for the manufacture of A -transdehydroandrosterone, consisting in combining A -dehydroandrosterone of the formula stene-3,17-diol, consisting in combining A androstene-3,17-dio1 of the formula,

OH: OH:

with hydrogen halide and then eliminating the hydrogen halide under mild conditions with alkali metal salts of organic acids.

LEOPOLD RUZICKA. 

